Heart failure (HF) is the fastest growing cardiovascular condition in the United States and the most common reason for hospitalization among older adults. Symptoms are of utmost importance in HF because they drive urgent healthcare utilization and predict both health-related quality of life and clinical events. Our lac of understanding of the biological underpinnings of HF symptoms, however, is a prohibitive factor to progress in the development of effective therapies and interventions designed to mitigate symptom burden in HF. One critical gap in our knowledge of HF symptom biology is how symptoms are related to two known conditions of aging: physical frailty and senescence. Accordingly, the goal of this proposed research is to gain greater insight into HF symptom biology by examining measures of physical frailty and metrics of senescence as potential biological underpinnings of HF symptoms. We will address two specific aims by using data from a new cross-sectional cohort study on physical frailty in 70 adults with HF and by capitalizing on our existing data on replicative and metabolic senescence and symptoms among adults with HF. Our two aims are to 1) quantify associations among measures of physical frailty and physical symptoms among adults with HF, and 2) quantify associations among metrics of replicative and metabolic senescence and physical symptoms among adults with HF. This innovative research will be the first to assess measures of physical frailty and metrics of senescence as they relate to HF symptoms as a step towards enhancing our understanding of HF symptom biology and will provide foundational knowledge to advance the clinical management of HF symptoms and to support optimal patient outcomes. Additionally, as part of a National Research Service Award proposal, this study will contribute to the long-term goal of developing the applicant into an independent and productive nurse scientist with an influential program of research centered on HF symptom biology. This proposed research and fellowship training draw on the combined expertise of an exemplary interdisciplinary team that brings together content and analytic expertise and clinical relevance. In sum, the results of this proposed fellowship are directly aligned with the goals of the National Institute of Nursing Research through an enhanced understanding of HF symptoms as they relate to conditions of biological aging and the facilitation of the development of the next generation of nurse scientists